The overall objective is to investigate the consequences of the aging process on functional characteristics of peptidergic neuronal systems in the human brain. Aging is associated with generalized degeneration of brain functions, as reflected by alterations in neuroendocrine systems, autonomic processes, and cognition. Of specific interest are neuronal systems in brain containing luteinizing hormone releasing hormone (LHRH) and thyrotropin releasing hormone (TRH), both of which, in addition to their roles in regulating anterior pituitary function, have been proposed to participate in important brain functions including control of sexual behavior, temperature regulation, libido, mood, and others. In this proposal, studies are set forth to define many characteristics of the LHRH and TRH neuronal systems of the adult human brain and further, to determine what alterations in these systems are associated with aging. The first objective of this investigation will be to define the levels of LHRH and TRH within the hypothalamus and extra-hypothalamic brain regions of men and women throughout life. Since functional changes in neuronal sustems may occur even though tissue contents might be constant, the subcellular localization and subsynaptosomal storage pools of LHRH and TRH in brain tissues will also be investigated as a function of age in men and women. A second objective of this proposal will be to investigate the effects of aging on the secretory activity of LHRH and TRH containing neurons. The effects of ions and neurotransmitters on in vitro secretion of LHRH and TRH from hypothalamic nerve terminals of young and aged men and women will be investigated. The activity of a neuronal system is reflected not only by the synthesis, storage, and release of neurotransmitter substances, but also by the responsiveness of its efferent limb, i.e., the post synaptic site of action. Therefore, as a third objective, the presence and characteristics of receptors for LHRH and TRH in brain tissues of young and aged persons will be investigated. Special emphasis will be placed on ascertaining whether the distribution, density, and/or kinetic parameters of receptor binding are altered during aging.